The recent conference for the Society for Neuroscience gave many BRAIN Initiative-funded researchers the chance to showcase their newly developed technologies that are helping to drive neuroscience forward. Nearly 30,000 people from 75 countries attended the meeting, held October 19-23 in Chicago, Illinois.
Recent success stories from BRAIN-funded investigators include: Dr. Matthew Tantam’s lab engineered genetically-fluorescent sensors that allow for high-resolution, real-time, and live-cell imaging of ATP dynamics; Dr. Anne Churchland and team showed that animals execute expert decisions while performing richly varied, uninstructed movements that profoundly shape neural activity, as measured by two-photon imaging and Neuropixels electrophysiological probes; a clinical trial of an experimental brain device, developed in the lab of Dr. Nader Pouratian, enables blind patients to better distinguish light and motion; and a new method developed by Dr. Edward Chang and team use brain activity to reconstruct human speech. With these scientific advances and many others, the BRAIN Initiative has made important progress in advancing our understanding of the brain.
BRAIN-related events at Neuroscience 2019 included a mini-symposium, a social, neuroethics sessions, and a myriad of talks and poster presentations. For instance, the National Institutes of Health (NIH) presented a poster on Sunday, highlighting how the agency has been contributing to funding and strategic planning for the BRAIN Initiative. The NIH provides several avenues of funding at multiple career levels in order to promote the development of cutting-edge technology. Along with other federal and private institutions, the NIH participates in the BRAIN Initiative Alliance to help communicate BRAIN advances and helps host an annual meeting for all researchers funded by BRAIN.
All of the BRAIN-associated activities at Neuroscience 2019 allowed scientists to highlight how the BRAIN Initiative has helped support the development of game-changing tools and resources. Many of these new technologies are already beginning to be distributed to the wider neuroscience community.
A primary objective of the BRAIN Initiative is to disseminate tools to other researchers in order to accomplish the Initiative’s research goals. Dr. Walter Koroshetz, Director of the National Institute of Neurological Disorders and Stroke (NINDS), chaired a mini-symposium on Saturday that highlighted the work of BRAIN-funded scientists. “BRAIN Initiative: Cutting-Edge Tools and Resources for the Community” featured six researchers who have developed and disseminated new technology that is helping to drive neuroscience forward.
“We are preparing and entering the second half of the BRAIN Initiative,” said Dr. Koroshetz. “The focus remains the same: to understand how brain circuit function enables everything we do, and how disordered brain circuits contribute to neurological, mental, and substance use disorders.”
Jeff Lichtman, PhD, of Harvard University, showcased his BRAIN-funded work to develop and share tools to allow researchers to better visualize neural connections. His talk, “A Facility to Generate Connectomics Information,” described how his lab uses serial section electron microscopy to get a highly accurate view of the location of cells and synapses within a 3D volume. His team has used this technique to view the overarching patterns of connectivity of different cell types within the human cortex. Dr. Lichtman also shares his devices and computer infrastructure with other labs so that other neuroscience investigators can do their own studies on connectivity with other types of brain tissue.
The next talk, “High-Throughput Methods for Fluorescence-Based Connectomics,” featured new tools to better visualize synapses. Alison L. Barth, PhD, of Carnegie Mellon University, described connecting anatomical data with functional data to better understand how brain circuits change over time, following learning, or in disease states. Her lab has developed genetically-expressed fluorescent labeling reagents and software programs that can accurately detect different types of synapses at high resolution. The Barth lab and colleagues share some of these technologies through sites like Addgene and GitHub.
How does the hippocampus retrieve sensory information that is stored in different regions across the brain in order to construct a memory? The lab of Loren Frank, PhD, of the Kavli Foundation, HHMI, and the University of California, San Francisco, has been developing new devices to help answer this question. In order to get large-scale recordings of brain activity, Dr. Frank and colleagues have developed a new type of very thin, flexible polymer probe. When paired with the lab’s innovative algorithms, these probes can simultaneously capture readings from 1024 electrodes in order to better understand how entire populations of neurons communicate with each other. Their technology also enables investigators to collect stable brain recordings over the course of several months.
Kristen Harris, PhD, of the University of Texas at Austin, presented “Enhanced Resolution of 3DEM Analysis of Synapses.” Her lab has developed new techniques for 3D imaging, including combining tilt tomography and electron microscopy in order to get better resolution of cell borders. The Harris lab has also developed a collection of software and protocols to more accurately visualize and measure the structure of synapses. Many of these tools, as well as public datasets, are available to other researchers at 3DEM.org.
How can connectivity information be used to help people? Kathleen Gates, PhD, from the University of North Carolina at Chapel Hill, discussed a new method for identifying patterns of connectivity among different subsets of people. Her talk, “Introducing an Unsupervised Classification Tool: Separating Individuals Based on Within- or Between Network Functional Brain Activity,” described a cutting-edge tool, Group Iterative Multiple Model Estimation (GIMME), that is able to accurately separate people into subgroups based on brain functional connectivity maps. The Gates lab offers several software and data analysis packages, a GitHub page, and online tutorials to other interested researchers.
The final talk, “Renewable Recombinant Immunolabels Developed and Validated for BRAIN Research,” was by James Trimmer, PhD, of the University of California, Davis. His lab’s goal is to create, validate, and disseminate effective and low-cost monoclonal antibodies to be used by the neuroscience community. Additionally, the Trimmer lab is in the process of cloning and validating recombinant antibody fragments that can be expressed from plasmids for in vitro antibody production, which makes it easier to use and share validated, mutation-free antibody clones. So far, his lab has distributed over 60,000 vials of monoclonal antibodies, has made available 500 validated hybridoma cell lines, and has disseminated 100 recombinant monoclonal antibody-expressing plasmids through Addgene.
BRAIN Initiative Alliance Social
Many researchers turned out on Sunday night for “Tools & Tech: A BRAIN Initiative Alliance Social,” an event that fostered new collaborations and facilitated access to cutting-edge tools for people in the neuroscience community.
Several researchers presented software programs designed to better capture, process, or use neuroscience data. One such tool was cytoNet, software developed by the Amina Ann Qutub lab from the University of Texas, San Antonio. This web-based program measures the spatial organization of cells in 2D culture to get a better sense of how cell networks change over time or in response to certain stimuli. “This is software that captures cell community through microscope images,” said Dr. Arun Mahadevan, who helped develop this technology over the course of his PhD at Rice University.
Other software at the social included tools from the Translational NeuroEngineering lab at the University of Minnesota, which uses real-time recordings of brain signals paired with automated stimulation in order to manipulate communication between two brain regions, and Neurodata Without Borders, an ecosystem of tools that helps store, consolidate, process, and analyze large neurophysiology datasets.
Some investigators showcased new electrodes and probes (see left image). “We’re using 3D printing to make the next generation of brain probes,” said Sandy Ritchie, a PhD candidate at Carnegie Mellon University. She works in the Advanced Manufacturing and Materials Laboratory, led by Dr. Rahul Panat, which is innovating new manufacturing techniques to solve neuroscience problems. This team can very quickly produce microelectrode arrays that allow scientists to access layers of the brain that were previously out of reach. Dr. Panat said that these probes “can increase the recording density by one order of magnitude, allow greater customization, and integrate stimulation with recording in three dimensions.”
A team of researchers from the University of Michigan presented silicon electrodes paired with LEDs for in vivo research that could provide close to single-neuron stimulation. This technology, as well as several other tools, is being disseminated across the neuroscience community through the Multimodal Integrated NeuroTechnology (MINT) NeuroNex program.
Still more groups built new hardware that can change the way researchers interact with the brain. Scientists from the University of Minnesota, Twin Cities, in the Biosensing and Biorobotics Laboratory led by Dr. Suhasa Kodandaramaiah, developed a robotics platform that can perform microsurgeries on mice. Craniobot is a useful tool for implementing very precise, delicate procedures (see right image). The robot’s software is open-source and the hardware can be built for under $1,500 using protocols from the lab and materials from Amazon. This lab has also developed “See-Shells,” transparent polymer mouse skulls that enable long-term brain imaging.
This social helped engage the community and brought together researchers across multiple disciplines in order to make new connections, educate people about the advances being made through the BRAIN Initiative, and help scientists find new tools, resources, and opportunities for advancing neuroscience research.
Neuroethics at Neuroscience 2019
Neuroethics is a field that studies the ethical, legal, and societal implications of neuroscience. Nita Farahany, JD, PhD, professor at Duke University, President of the International Neuroethics Society, and a member of the NIH BRAIN Initiative’s Neuroethics Working Group (NEWG), gave the annual David Kopf Lecture on Neuroethics at Neuroscience 2019. She challenged attendees to consider the ethical, legal, and social ramifications of proliferation of technologies to access functioning of the human brain. Dr. Farahany described various devices that currently can measure mood and decode simple numbers, shapes, or words a person is saying, hearing, or seeing. She also discussed various instances where corporations are already using such devices to monitor their employees, to determine access to desirable consumer goods, and to monitor school children. Dr. Farahany shared data suggesting that people don’t fully understand the capabilities or implications of these evolving brain-recording technologies. She argued for a pro-active broad deliberation on how to protect what she refers to as ‘cognitive liberty’, in a potential future where neurotechnology is in widespread use.
Dr. Khara Ramos, Director of the Neuroethics Program at NINDS, presented the poster “Neuroethics: An Essential Partner to Enhance the NIH BRAIN Initiative” at Neuroscience 2019. Her presentation highlighted how neuroethics can serve to anticipate and address ethical questions raised by neuroscience research and that integrating neuroethics into a neuroscience research project can be a powerful way to maximize positive impact of the research. New tools and technologies that are being used to study the brain may raise important neuroethical challenges. For example: If collecting and sharing neural data is crucial, how does this intersect with protecting participants’ privacy? How do patients’ and investigators’ perceptions of the risks and benefits of data sharing align or differ?
The NIH has a multi-part strategy to help manage the neuroethical implications of the development and application of BRAIN-funded tools and technologies. This Neuroethics program includes funding neuroethics research projects, hosting workshops that focus on neuroethical considerations in specific areas of BRAIN-funded research, and managing the NEWG, who have published guidance on key ethical challenges associated with BRAIN-funded research.
“I hope this is just the beginning of a culture change, in that neuroethics will become a routine part of neuroscience training programs, and neuroscientists will become quite comfortable with integrating neuroethics into their research programs,” Dr. Ramos said.
Dr. Winston Chiong, Associate Professor, University of California, San Francisco, and a member of the NIH BRAIN NEWG, co-chaired with Dr. Ramos the Neuroethics Social at Neuroscience 2019. This event was open to all conference attendees and highlighted the ways in which researchers and educators could incorporate neuroethics concepts into various stages of neuroscience training. Featured guests from multiple institutions helped attendees explore how training programs, facilities, and laboratories could use neuroethics education to help researchers better pursue the ethical dimensions of their neuroscience work.
The BRAIN Initiative Beyond Neuroscience 2019
Many new reagents, imaging devices, probes, protocols, data processing packages, and software tools are now available to the neuroscience community due to the investments of the BRAIN Initiative. This initiative will continue to fund cutting-edge research into new tools and resources and offer opportunities for scientists to form collaborations that allow them to apply these tools to new research questions.
Staying up-to-date on the latest BRAIN Initiative advancements is possible thanks to the work of the BRAIN Initiative Alliance (BIA), a group consisting of the National Institutes of Health, the National Science Foundation, the Intelligence Advanced Research Projects Activity, the Food and Drug Administration, Kavli Foundation, Simons Foundation, Allen Institute, and the Institute of Electrical and Electronic Engineers. Scientists wishing to learn more can visit www.braininitiative.org/ for more information on funding opportunities, BRAIN Initiative goals, and updates on new research, or follow the BIA on Facebook (https://www.facebook.com/usBRAINInitiative/) or Twitter (https://twitter.com/USBrainAlliance).